Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model

NEUROBIOLOGY OF DISEASE

卷:59

Article

Li, Wenjun¹  Huang, Renqi¹  Shetty, Ritu A.¹  Thangthaeng, Nopporn¹  Liu, Ran¹  Chen, Zhenglan¹  Sumien, Nathalie¹  Rutledge, Margaret¹  Dillon, Glenn H.²  Yuan, Fang³  Forster, Michael J.¹  Simpkins, James W.²  Yang, Shao-Hua^1,3 

[1] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA

[2] W Virginia Univ, Hlth Sci Ctr, Ctr Neurosci, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA

[3] Capital Med Univ, Beijing Tiantan Hosp, Beijing Neurosurg Inst, Dept Neurosurg, Beijing 100050, Peoples R China

关键词: Stroke;    Long term potentiation;    Hippocampus;    Vascular dementia;    Cognition;    GABA;    ERK;   

DOI  :  10.1016/j.nbd.2013.06.014

来源: Elsevier

【 摘 要 】

Vascular dementia ranks as the second leading cause of dementia in the United States. However, its underlying pathophysiological mechanism is not fully understood and no effective treatment is available. The purpose of the current study was to evaluate long-term cognitive deficits induced by transient middle cerebral artery occlusion (tMCAO) in rats and to investigate the underlying mechanism. Sprague-Dawley rats were subjected to tMCAO or sham surgery. Behavior tests for locomotor activity and cognitive function were conducted at 7 or 30 days after stroke. Hippocampal long term potentiation (LTP) and involvement of GABAergic neurotransmission were evaluated at 30 days after sham surgery or stroke. Immunohistochemistry and Western blot analyses were conducted to determine the effect of tMCAO on cell signaling in the hippocampus. Transient MCAO induced a progressive deficiency in spatial performance. At 30 days after stroke, no neuron loss or synaptic marker change in the hippocampus were observed. LTP in both hippocampi was reduced at 30 days after stroke. This LTP impairment was prevented by blocking GABA(A) receptors. In addition, ERK activity was significantly reduced in both hippocampi. In summary, we identified a progressive decline in spatial learning and memory after ischemic stroke that correlates with suppression of hippocampal LTP, elevation of GABAergic neurotransmission, and inhibition of ERK activation. Our results indicate that the attenuation of GABAergic activity or enhancement of ERK/MAPK activation in the hippocampus might be potential therapeutic approaches to prevent or attenuate cognitive impairment after ischemic stroke. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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